We evaluated the shift in the characteristics of people who received interferon-based hepatitis C virus (HCV) treatments and those who received recently introduced direct-acting antivirals (DAAs) in British Columbia (BC), Canada. The BC Hepatitis Testers Cohort includes 1.5 million individuals tested for HCV or HIV, or reported cases of hepatitis B and active tuberculosis in BC from 1990 to 2013 linked to medical visits, hospitalization, cancer, prescription drugs and mortality data. This analysis included all patients who filled at least one prescription for HCV treatment until 31 July 2015. HCV treatments were classified as older interferon-based treatments including pegylated interferon/ribavirin (PegIFN/RBV) with/without boceprevir or telaprevir, DAAs with RBV or PegIFN/RBV, and newer interferon-free DAAs. Of 11 886 people treated for HCV between 2000 and 2015, 1164 (9.8%) received interferon-free DAAs (ledipasvir/sofosbuvir: n=1075; 92.4%), while 452 (3.8%) received a combination of DAAs and RBV or PegIFN/RBV. Compared to those receiving interferon-based treatment, people with HIV co-infection (adjusted odds ratio [aOR]: 2.96, 95% CI: 2.31-3.81), cirrhosis (aOR: 1.77, 95% CI: 1.45-2.15), decompensated cirrhosis (aOR: 1.72, 95% CI: 1.31-2.28), diabetes (aOR: 1.30, 95% CI: 1.10-1.54), a history of injection drug use (aOR: 1.34, 95% CI: 1.09-1.65) and opioid substitution therapy (aOR: 1.30, 95% CI: 1.01-1.67) were more likely to receive interferon-free DAAs. Socio-economically marginalized individuals were significantly less likely (most deprived vs most privileged: aOR: 0.71, 95% CI: 0.58-0.87) to receive DAAs. In conclusion, there is a shift in prescription of new HCV treatments to previously excluded groups (eg HIV-co-infected), although gaps remain for the socio-economically marginalized populations.
People remain at risk of reinfection with hepatitis C virus (HCV), even after clearance of the primary infection. We identified factors associated with HCV reinfection risk in a large population-based cohort study in British Columbia, Canada, and examined the association of opioid substitution therapy and mental health counselling with reinfection.
We obtained data from the British Columbia Hepatitis Testers Cohort, which includes all individuals tested for HCV or HIV at the British Columbia Centre for Disease Control Public Health Laboratory during 1990–2013 (when data were available). We defined cases of HCV reinfection as individuals with a positive HCV PCR test after either spontaneous clearance (two consecutive negative HCV PCR tests spaced ≥28 days apart without treatment) or a sustained virological response (SVR; two consecutive negative HCV PCR tests spaced ≥28 days apart 12 weeks after completing interferon-based treatment). We calculated incidence rates of HCV reinfection (per 100 person-years of follow-up) and corresponding 95% CIs assuming a Poisson distribution, and used a multivariable Cox proportional hazards model to examine reinfection risk factors (age, birth cohort, sex, year of HCV diagnosis, HCV clearance type, HIV co-infection, number of mental health counselling visits, levels of material and social deprivation, and alcohol and injection drug use), and the association of opioid substitution therapy and mental health counselling with HCV reinfection among people who inject drugs (PWID).
5915 individuals with HCV were included in this study after clearance (3690 after spontaneous clearance and 2225 after SVR). 452 (8%) patients developed reinfection; 402 (11%) after spontaneous clearance and 50 (2%) who had achieved SVR. Individuals were followed up for a median of 5·4 years (IQR 2·9–8·7), and the median time to reinfection was 3·0 years (1·5–5·4). The overall incidence rate of reinfection was 1·27 (95% CI 1·15–1·39) per 100 person-years of follow-up over a total of 35 672 person-years, with significantly higher rates in the spontaneous clearance group (1·59, 1·44–1·76) than in the SVR group (0·48, 0·36–0·63). With the adjusted Cox proportional hazards model, we noted higher reinfection risks in the spontaneous clearance group (adjusted hazard ratio [HR] 2·71, 95% CI 2·00–3·68), individuals co-infected with HIV (2·25, 1·78–2·85), and PWID (1·53, 1·21–1·92) than with other reinfection risk factors. Among the 1604 PWID with a current history of injection drug use, opioid substitution therapy was significantly associated with a lower risk of reinfection (adjusted HR 0·73, 95% CI 0·54–0·98), as was engagement with mental health counselling services (0·71, 0·54–0·92).
The incidence of HCV reinfection was higher among HIV co-infected individuals, those who spontaneously cleared HCV infection, and PWID. HCV treatment complemented with opioid substitution therapy and mental health counselling could reduce HCV reinfection risk among PWID. These findings support policies of post-clearance follow-up of PWID, and provision of harm-reduction services to minimise HCV reinfection and transmission.
Blood pressure abnormalities may play an important role in macrovascular damage in type 1 diabetes. Little is known about blood pressure abnormalities and macrovascular damage in children with type 1 diabetes.
Children with type 1 diabetes (n = 57) for a short (3 months‐2 years; n = 24) or long duration (≥5 years; n = 33) and a group of control children without diabetes (n = 29) completed 24‐h ambulatory blood pressure monitoring (ABPM). Carotid intima media thickness (cIMT), a subclinical indicator of atherosclerosis, was assessed by carotid ultrasound.
ABPM abnormalities were more prevalent (57% vs 24%, respectively), and daytime, nighttime and 24‐h systolic, diastolic, and mean arterial blood pressure indices were higher in children with type 1 diabetes compared to control children. The odds estimate of an ABPM abnormality was 6.68 (95% confidence interval: 1.95, 22.9; P = .003) in children with type 1 diabetes compared to controls after adjusting for age, sex, and BMI standardized for age and sex (zBMI). An interaction between ABPM and zBMI on cIMT was observed. In children with type 1 diabetes and ABPM abnormalities, every 1 SD increase in zBMI was associated with a 0.030 mm increase in cIMT (95% confidence interval: 0.002, 0.041; P = .031). This was not observed in control children with ABPM abnormalities or in children with normal ABPM, regardless of type 1 diabetes status.
Children with type 1 diabetes have a high prevalence of ABPM abnormalities independent of disease duration and this is related to early indicators of cardiovascular damage.
Indications for insulin pump therapy (IPT) in children with type 1 diabetes (T1D) are relatively non-specific and therefore subject to provider discretion. Health professionals' perceptions of which people will have difficulty with IPT, for example, those with higher hemoglobin A1c (HbA1c ), may not be correct. This study examined the effect of IPT on HbA1c , and the role of pre-pump HbA1c on this effect.
All children with T1D started on IPT at British Columbia Children's Hospital from January 2011 through June 2016 were included if they had HbA1c values available both before and after IPT (n = 125). Generalized estimating equations was used to estimate the effects of IPT on HbA1c , stratified by pre-pump HbA1c levels (good: <7.5% [<58 mmol/mol], moderate: 7.5%-9.0% [58-75 mmol/mol], poor: >9.0% [>75 mmol/mol]).
After adjusting for potential confounders, mean HbA1c decreased by 0.48% [5.2 mmol/mol] (95% confidence interval: -0.64, -0.33% [-7.0, -3.6 mmol/mol]; P < 0.0001) after IPT initiation. The adjusted mean HbA1c decreased by 0.14% [1.5 mmol/mol] (-0.35, 0.07% [-3.8, 0.8 mmol/mol]; P = 0.188), 0.54% [5.9 mmol/mol] (-0.74, -0.34% [-8.1, -3.7 mmol/mol]; P < 0.0001), and 1.08% [11.8 mmol/mol] (-1.69, -0.46% [-18.5, -5.0 mmol/mol]; P = 0.0006) after pump initiation in the good, moderate, and poor pre-pump metabolic control groups, respectively.
Pre-pump HbA1c appears to play a significant role in the effects of IPT on HbA1c , with the largest decrease in HbA1c seen in the poor pre-pump HbA1c group. Eligibility and consideration for IPT should be expanded to routinely include these children.
Summary Background Global development goals increasingly rely on country-specific estimates for benchmarking a nation's progress. To meet this need, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 estimated global, regional, national, and, for selected locations, subnational cause-specific mortality beginning in the year 1980. Here we report an update to that study, making use of newly available data and improved methods. GBD 2017 provides a comprehensive assessment of cause-specific mortality for 282 causes in 195 countries and territories from 1980 to 2017. Methods The causes of death database is composed of vital registration (VR), verbal autopsy (VA), registry, survey, police, and surveillance data. GBD 2017 added ten VA studies, 127 country-years of VR data, 502 cancer-registry country-years, and an additional surveillance country-year. Expansions of the GBD cause of death hierarchy resulted in 18 additional causes estimated for GBD 2017. Newly available data led to subnational estimates for five additional countries—Ethiopia, Iran, New Zealand, Norway, and Russia. Deaths assigned International Classification of Diseases (ICD) codes for non-specific, implausible, or intermediate causes of death were reassigned to underlying causes by redistribution algorithms that were incorporated into uncertainty estimation. We used statistical modelling tools developed for GBD, including the Cause of Death Ensemble model (CODEm), to generate cause fractions and cause-specific death rates for each location, year, age, and sex. Instead of using UN estimates as in previous versions, GBD 2017 independently estimated population size and fertility rate for all locations. Years of life lost (YLLs) were then calculated as the sum of each death multiplied by the standard life expectancy at each age. All rates reported here are age-standardised. Findings At the broadest grouping of causes of death (Level 1), non-communicable diseases (NCDs) comprised the greatest fraction of deaths, contributing to 73·4% (95% uncertainty interval [UI] 72·5–74·1) of total deaths in 2017, while communicable, maternal, neonatal, and nutritional (CMNN) causes accounted for 18·6% (17·9–19·6), and injuries 8·0% (7·7–8·2). Total numbers of deaths from NCD causes increased from 2007 to 2017 by 22·7% (21·5–23·9), representing an additional 7·61 million (7·20–8·01) deaths estimated in 2017 versus 2007. The death rate from NCDs decreased globally by 7·9% (7·0–8·8). The number of deaths for CMNN causes decreased by 22·2% (20·0–24·0) and the death rate by 31·8% (30·1–33·3). Total deaths from injuries increased by 2·3% (0·5–4·0) between 2007 and 2017, and the death rate from injuries decreased by 13·7% (12·2–15·1) to 57·9 deaths (55·9–59·2) per 100 000 in 2017. Deaths from substance use disorders also increased, rising from 284 000 deaths (268 000–289 000) globally in 2007 to 352 000 (334 000–363 000) in 2017. Between 2007 and 2017, total deaths from conflict and terrorism increased by 118·0% (88·8–148·6). A greater reduction in total deaths and death rates was observed for some CMNN causes among children younger than 5 years than for older adults, such as a 36·4% (32·2–40·6) reduction in deaths from lower respiratory infections for children younger than 5 years compared with a 33·6% (31·2–36·1) increase in adults older than 70 years. Globally, the number of deaths was greater for men than for women at most ages in 2017, except at ages older than 85 years. Trends in global YLLs reflect an epidemiological transition, with decreases in total YLLs from enteric infections, respiratory infections and tuberculosis, and maternal and neonatal disorders between 1990 and 2017; these were generally greater in magnitude at the lowest levels of the Socio-demographic Index (SDI). At the same time, there were large increases in YLLs from neoplasms and cardiovascular diseases. YLL rates decreased across the five leading Level 2 causes in all SDI quintiles. The leading causes of YLLs in 1990—neonatal disorders, lower respiratory infections, and diarrhoeal diseases—were ranked second, fourth, and fifth, in 2017. Meanwhile, estimated YLLs increased for ischaemic heart disease (ranked first in 2017) and stroke (ranked third), even though YLL rates decreased. Population growth contributed to increased total deaths across the 20 leading Level 2 causes of mortality between 2007 and 2017. Decreases in the cause-specific mortality rate reduced the effect of population growth for all but three causes: substance use disorders, neurological disorders, and skin and subcutaneous diseases. Interpretation Improvements in global health have been unevenly distributed among populations. Deaths due to injuries, substance use disorders, armed conflict and terrorism, neoplasms, and cardiovascular disease are expanding threats to global health. For causes of death such as lower respiratory and enteric infections, more rapid progress occurred for children than for the oldest adults, and there is continuing disparity in mortality rates by sex across age groups. Reductions in the death rate of some common diseases are themselves slowing or have ceased, primarily for NCDs, and the death rate for selected causes has increased in the past decade. Funding Bill & Melinda Gates Foundation.
Direct-acting antiviral therapies (DAA) are an important tool for hepatitis C virus (HCV) elimination. However, reinfection among people who inject drugs (PWID) may hamper elimination targets. We therefore estimated HCV reinfection rates among DAA-treated individuals, including PWIDs.
We analyzed data from the BC Hepatitis Testers Cohort which included ∼1.7 million individuals screened for HCV in British Columbia, Canada. We followed HCV-infected individuals treated with DAAs who achieved a sustained virologic response (SVR) and had ≥1 subsequent HCV RNA measurement to April 22nd, 2018. Reinfection was defined as a positive RNA measurement after SVR. PWIDs were identified using a validated algorithm and classified based on recent (<3 years) or former (≥3 years before SVR) use. Crude reinfection rates per 100 person-years (PYs) were calculated. Poisson regression was used to model adjusted incidence rate ratios (IRRs) and 95% confidence intervals (CI).
Of 4,114 individuals who met inclusion, most were male (n=2,692, 65%), born before 1965 (n=3,411, 83%) and were either recent (n=875, 21%) or former PWIDs (n=1,793, 44%). Opioid-agonist therapy (OAT) was observed in 19% of PWIDs. We identified 40 reinfections during 2,767 PYs. Reinfection rates were higher among recent (3.1/100 PYs; IRR: 6.7, 95% CI: 1.9, 23.5) and former PWIDs (1.4/100 PYs; IRR: 3.7, 95% CI: 1.1, 12.9) than non-PWIDs (0.3/100 PYs). Among recent PWIDs, reinfection rates were higher among individuals born after 1975 (10.2/100 PYs) and those with co-infected with HIV (5.7/100 PYs). Only one PWID receiving daily OAT developed reinfection.
Population-level reinfection rates remain elevated after DAA therapy among PWIDs because of ongoing exposure risk. Engagement of PWIDs in harm-reduction and support services is needed to prevent reinfections.
We estimated HCV reinfection rates after successful treatment with direct-acting antiviral therapies. Our findings showed that the risk of reinfection was highest among people with recent injection drug use. Among people who inject drugs, daily use of opioid-agonist therapy was associated with a lower risk of reinfection.
To access care, pediatric type 1 diabetes (T1D) patients living in British Columbia (BC), Canada, travel to the sole tertiary pediatric hospital (BC Children's Hospital; BCCH), or they receive community care from pediatric endocrinologists and/or pediatricians. We sought to determine whether HbA1C and patient reported outcomes were associated with (i) distance to clinic and (ii) tertiary vs. community care.
Patients were recruited from T1D clinics across BC. Clinical chart review and patient surveys were completed, including the Diabetes Treatment Satisfaction Questionnaire (DTSQ). Clinic type was categorized as tertiary (BCCH) or community, and travel time to BCCH was categorized as <1 hour (h), 1-2h, or >2h.
There were 189 participants. Age and duration of T1D were similar across groups. Mean number of visits/year for BCCH groups were 2.23, 2.24 and 2.05 for the <1h, 1-2h and >2h groups, respectively, vs. 3.26 for the community group. Adjusted mean difference in HbA1C was +0.65% (95% CI 0.15, 1.15) and +0.52% (95% CI 0.02, 1.02) for the BCCH >2h group compared to BCCH <1h group and community group, respectively. Child DTSQ scores were significantly lower in the BCCH >2h group compared to the BCCH <1h and community groups.
Children travelling >2h to T1D clinic at BCCH had significantly higher HbA1C values and lower satisfaction with care versus those travelling <1h to BCCH and those receiving community care. Access to care closer to home may benefit glycemic control in children with T1D and improve treatment satisfaction. Future research should determine whether these findings can be replicated in other regions.
Introduction Behavioural and cognitive behavioural programmes are commonly used to assist with weight management, but there is considerable scope to improve their effectiveness, particularly in the longer term. Third-wave cognitive behaviour therapies (CBTs) have this potential and are increasingly used. This systematic review will assess the effect of third-wave CBTs for weight management on weight, psychological and physical health outcomes in adults with overweight or obesity.Methods and analysis The systematic review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidance. We will include studies of any third-wave CBTs focusing on weight loss or weight maintenance for adults with a body mass index (BMI) >=25kg/m2. Eligible study designs will be randomised control trials, non-randomised trials, prospective cohort and case series. Outcomes of interest will be body weight/BMI, psychological and physical health, and adherence. We will search the following databases from inception to 16 January 2018: MEDLINE, CINAHL, Embase, Cochrane database (CENTRAL), PsycINFO, AMED, ASSIA and Web of Science. The search strategy will be based on the concepts: (1) third-wave CBTs and (2) overweight, obesity or weight management. No restrictions will be applied. We will search reference lists of relevant reviews and included articles. Two independent reviewers will screen articles for eligibility using a two-stage process. Two independent reviewers will extract data, assess risk of bias using Risk of Bias 2.0, Risk of Bias in Non-randomised studies of Interventions or Risk of Bias in Non-randomised Studies of Exposures checklist and assess quality using the Grading of Recommendations Assessment, Development and Evaluation tool. A random-effects network meta-analysis of outcomes, and sub-group analyses and meta-regression will be conducted, where data permit. If not appropriate, a narrative synthesis will be undertaken.Ethics and dissemination Ethical approval is not required as no primary data will be collected. The completed systematic review will be disseminated in a peer-reviewed journal, presented at conferences and used to inform the development of a weight management programme.PROSPERO registration number CRD42018088255.
Large linked healthcare administrative datasets could be used to monitor programs providing prevention and treatment services to people who inject drugs (PWID). However, diagnostic codes in administrative datasets do not differentiate non-injection from injection drug use (IDU). We validated algorithms based on diagnostic codes and prescription records representing IDU in administrative datasets against interview-based IDU data.
The British Columbia Hepatitis Testers Cohort (BC-HTC) includes ∼1.7 million individuals tested for HCV/HIV or reported HBV/HCV/HIV/tuberculosis cases in BC from 1990 to 2015, linked to administrative datasets including physician visit, hospitalization and prescription drug records. IDU, assessed through interviews as part of enhanced surveillance at the time of HIV or HCV/HBV diagnosis from a subset of cases included in the BC-HTC (n = 6559), was used as the gold standard. ICD-9/ICD-10 codes for IDU and injecting-related infections (IRI) were grouped with records of opioid substitution therapy (OST) into multiple IDU algorithms in administrative datasets. We assessed the performance of IDU algorithms through calculation of sensitivity, specificity, positive predictive, and negative predictive values.
Sensitivity was highest (90–94%), and specificity was lowest (42–73%) for algorithms based either on IDU or IRI and drug misuse codes. Algorithms requiring both drug misuse and IRI had lower sensitivity (57–60%) and higher specificity (90–92%). An optimal sensitivity and specificity combination was found with two medical visits or a single hospitalization for injectable drugs with (83%/82%) and without OST (78%/83%), respectively. Based on algorithms that included two medical visits, a single hospitalization or OST records, there were 41,358 (1.2% of 11–65 years individuals in BC) recent PWID in BC based on health encounters during 3- year period (2013–2015).
Algorithms for identifying PWID using diagnostic codes in linked administrative data could be used for tracking the progress of programing aimed at PWID. With population-based datasets, this tool can be used to inform much needed estimates of PWID population size.